The goal of this program is to define the mechanism of the activation of the first component of complement. Emphasis is being placed on the events involved in the proteolytic conversion of Cl proesterase to Cl esterase. A systematic approach to this problem has been undertaken in accordance with the following specific objectives: (1) Purification of human Cl esterase; (2) Enzymatic characterization of Cl esterase; (3) Purification of human Cl proesterase; (4) Measurement of enzymatic activity intrinsic to Cl proesterase; and (5) Kinetic analysis of Cl proesterase activation.